The Ras protooncogenes play a fundamental role in the control of cell growth and differentiation. The importance of this control is highlighted by the frequency of association of mutationally activated Ras with human tumors. The long-term goal of this research project is to contribute to our understanding of the mechanisms by which Ras modulates cell proliferation. Our focus is on elucidating the nature of the dominant Ras effector pathways that mediate oncogenic Ras-induced growth and morphological transformation. A better understanding of these pathways is an important step in the search for therapeutic strategies to control onset and progression of cancer. Our specific aims are: 1) to characterize a novel Ras effector pathway that contributes to regulation of cyclin D1 and NFkappaB via activation of Ral GTPases, 2) to assess the contribution of newly identified Ras-interacting proteins to Ras-mediated ell regulation, and 3) to explore the physical organization of Ras effector pathways as a means of regulating the specificity of signal transduction.